Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
The management of SIADH should be based on symptom severity and serum sodium levels, with fluid restriction as first-line therapy for mild to moderate cases and hypertonic saline for severe symptomatic cases. 1, 2
Diagnosis
- SIADH is characterized by hyponatremia (serum sodium < 134 mEq/L), hypoosmolality (plasma osmolality < 275 mosm/kg), inappropriately high urine osmolality (> 500 mosm/kg), and high urinary sodium concentration (> 20 mEq/L) in the absence of hypothyroidism, adrenal insufficiency, or volume depletion 1
- Assessment of volume status is critical to differentiate SIADH (euvolemic) from other causes of hyponatremia such as cerebral salt wasting (hypovolemic) 1
- A serum uric acid level < 4 mg/dL in the presence of hyponatremia has a positive predictive value for SIADH of 73-100% 1
Treatment Algorithm Based on Severity
Severe Symptomatic Hyponatremia (seizures, coma)
- Transfer to ICU for close monitoring 1
- Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 1, 2
- Monitor serum sodium every 2 hours initially 1
- Total correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2
- For patients with malnutrition, alcoholism, or advanced liver disease, use more cautious correction rates (4-6 mmol/L per day) 2
Mild Symptomatic or Asymptomatic Hyponatremia (Na < 120 mEq/L)
- Fluid restriction to 1 L/day is the cornerstone of treatment 1, 2
- Avoid fluid restriction during the first 24 hours of therapy to prevent overly rapid correction 3
- If no response to fluid restriction, add oral sodium chloride 2
- For chronic SIADH when fluid restriction is ineffective or poorly tolerated, consider demeclocycline as second-line treatment 1, 4
Moderate Hyponatremia (Na 120-125 mmol/L)
Pharmacological Options
Tolvaptan (vasopressin receptor antagonist):
- Indicated for clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction) 3
- Must be initiated in a hospital setting where serum sodium can be closely monitored 3
- Starting dose is 15 mg once daily, may increase to 30 mg after 24 hours, maximum 60 mg daily 3
- Do not administer for more than 30 days to minimize risk of liver injury 3
- Contraindicated in hypovolemic hyponatremia 3
- Avoid fluid restriction during first 24 hours of therapy 3
Demeclocycline: Second-line treatment for chronic SIADH when fluid restriction is ineffective 1, 4
Fludrocortisone: Primarily studied in neurosurgical patients, particularly those with subarachnoid hemorrhage at risk for vasospasm 1, 2
Urea: Considered an effective and safe treatment for SIADH 5
Special Considerations
- In neurosurgical patients with subarachnoid hemorrhage at risk for vasospasm, fluid restriction should be avoided 1, 2
- In SCLC patients with paraneoplastic SIADH, treatment of the underlying malignancy is important alongside hyponatremia management 1
- Hyponatremia usually improves after successful treatment of the underlying cause of SIADH 1
Monitoring and Follow-up
- For severe symptoms: monitor serum sodium every 2 hours during initial correction 1, 2
- For tolvaptan treatment, measure serum sodium after 0,6,24, and 48 hours of treatment to prevent overly rapid correction 6
- When discontinuing tolvaptan therapy for longer than 5-6 days, monitor for hyponatremic relapse 6
Common Pitfalls to Avoid
- Overly rapid correction leading to osmotic demyelination syndrome (dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma) 1, 2
- Inadequate monitoring during active correction 1, 2
- Using fluid restriction in cerebral salt wasting instead of SIADH 1, 2
- Failing to recognize and treat the underlying cause 1, 2
- Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 2